Gene regulation will be studied in two bacterial systems: (1) The control of a viral gene (integrase) that splices the viral genes into the host chromosome will be determined. (2) Regulation of the genes controlling synthesis of the vitamin biotin will be studied. The basic interest of both systems comes from the degree and type of internal complexity in the structure of the basic units of regulation (the operons) that their study has revealed. The principal method to be used is the isolation of variants in which new operons are created (and/or old ones interrupted) by deletion mutations or by genetic insertions (insertion sequences, tetracycline transposons, or mutator phage Mu-1). Specifically, deletions fusing the integrase gene of bacteriophage lambda to the bacterial tryptophan promoter and the biotin promoters to the lacZ gene will be used. The mechanism by which one such element (IS1) mediates insertion of lambda will be studied. Regulatory mutations in biotin biosynthesis will be mapped, studied for gene complementation and their effect on the biotin-activating enzyme, holoenzyme synthetase.